The overall goal of this project is to understand the biochemical basis for selective cytotoxic effect of antimetabolites. The specific aim is to develop and evaluate the potential utility of biochemical tests for predicting the sensitivity of normal and tumor cells to selected antimetabolites. Studies such as pharmacokinetics of drugs, drug metabolism, and retention of the active metabolite(s), the relative role of the de novo and salvage pathways for nucleic acid synthesis and quantitative estimation of nucleoside and nucleotide pools are being carried out. In addition, the role of normal metabolites in the in vivo modification of antitumor activity and/or toxicity of antimetabolites is being evaluated. In this project, major emphasis is being placed on the need for the simultaneous evaluation of multiple critical parameters in individual cell types. BIBLIOGRAPHIC REFERENCES: Walczak, I., Preisler, H., Renick, J., and Rustum, Y.M.: Separation of Leukemic Marrow into Proliferative Subpopulations by Centrifugal Elutriation. Proc. ASCO, 1977. Bernacki, R., Sharma, M., Porter, N., Evans, M., Rustum, Y., and Korytnyk, W.: Membrane Sugar Analogs: Biochemical Characteristics, Metabolism and Anti-Tumor Activity of Several Acetylated Hexosamines. ICN-UCLA Symposium on Cell Surface Carbohydrates and Biological Recognition. Feb. 20-25, 1977, Keystone, Colorado.